Our aim is to define the basis and pathogenetic mechanism of differential cell injury and recovery caused by actinomycin D (AM) and related DNA-binding carcinocidal agents in various cell types in culture, in all of which AM is equally effective in suppressing transcription. In the ensuing period, attention will be given to: 1. the cytopathology of acute (in HeLa, KB, HEp2) and subacute (in Vero, MDBK etc.) lethal damage resulting from inhibition of RNA synthesis by greater than 70 percent, with reference to effects on energy metabolism, chromatin, cytomembranes and lysosomes and their enzymes, and cell adhesion. The cytoplasm of cells enucleated by cytochalasin will be compared. 2. To the cell cycle block caused by very low (0.004 micron-M) concentrations of AM, and to effects on cellular differentiation. 3. To the basis of division delay during recovery from AM toxicity. 4. To carcinogenic transformation in vitro caused by DNA-binding agents. Work will be completed on the stathmokinetic effects of 3'deoxyadenosine and the basis of its colchicine-like action. The differential effects of cytochalasin D on transformed and nontransformed cells in respect to nuclear proliferation, resistance, binding of H3-CD and cytotoxicity will be explored. BIBLIOGRAPHIC REFERENCES: Tannenbaum, J., Tanenbaum, S., Lo, L.W., Godman, G. and Miranda, A. Binding and subcellular localization of tritiated cytochalasin D. Exp. Cell Res. 91:47-56, 1975. Godman, G., Miranda, A., Deitch, A., and Tanenbaum, S. Action of cytochalasin D on cells of established lines. III. Zeiosis and movements at the cell surface. J. Cell Biol. 64:644-667, 1975.